ID TYSY_PNECA Reviewed; 297 AA. AC P13100; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1990, sequence version 1. DT 08-NOV-2023, entry version 109. DE RecName: Full=Thymidylate synthase; DE Short=TS; DE Short=TSase; DE EC=2.1.1.45; GN Name=THYA; OS Pneumocystis carinii. OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina; OC Pneumocystomycetes; Pneumocystaceae; Pneumocystis. OX NCBI_TaxID=4754; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2671992; DOI=10.1073/pnas.86.17.6503; RA Edman U., Edman J.C., Lundgren B., Santi D.V.; RT "Isolation and expression of the Pneumocystis carinii thymidylate synthase RT gene."; RL Proc. Natl. Acad. Sci. U.S.A. 86:6503-6507(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-210. RX PubMed=7728138; DOI=10.1111/j.1550-7408.1995.tb01536.x; RA Mazars E., Odberg-Ferragut C., Dei-Cas E., Fourmaux M.N., Aliouat E.M., RA Brun-Pascaud M., Mougeot G., Camus D.; RT "Polymorphism of the thymidylate synthase gene of Pneumocystis carinii from RT different host species."; RL J. Eukaryot. Microbiol. 42:26-32(1995). RN [3] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS). RX PubMed=10529228; DOI=10.1021/bi991610i; RA Anderson A.C., O'Neil R.H., DeLano W.L., Stroud R.M.; RT "The structural mechanism for half-the-sites reactivity in an enzyme, RT thymidylate synthase, involves a relay of changes between subunits."; RL Biochemistry 38:13829-13836(1999). CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 7,8- CC dihydrofolate + dTMP; Xref=Rhea:RHEA:12104, ChEBI:CHEBI:15636, CC ChEBI:CHEBI:57451, ChEBI:CHEBI:63528, ChEBI:CHEBI:246422; CC EC=2.1.1.45; CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. CC -!- SUBUNIT: Homodimer. CC -!- SIMILARITY: Belongs to the thymidylate synthase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M25415; AAA33802.1; -; Genomic_DNA. DR EMBL; S77510; AAB34157.1; -; Genomic_DNA. DR PIR; A33720; YXUNTP. DR PDB; 1CI7; X-ray; 2.60 A; A/B=1-297. DR PDB; 1F28; X-ray; 1.90 A; A/B/C/D=1-297. DR PDBsum; 1CI7; -. DR PDBsum; 1F28; -. DR AlphaFoldDB; P13100; -. DR SMR; P13100; -. DR BindingDB; P13100; -. DR ChEMBL; CHEMBL3085612; -. DR DrugBank; DB03541; 10-Propargyl-5,8-Dideazafolic Acid. DR DrugBank; DB03800; Deoxyuridine monophosphate. DR VEuPathDB; FungiDB:T552_03081; -. DR BRENDA; 2.1.1.45; 4924. DR UniPathway; UPA00575; -. DR EvolutionaryTrace; P13100; -. DR GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC. DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro. DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR CDD; cd00351; TS_Pyrimidine_HMase; 1. DR Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 1. DR HAMAP; MF_00008; Thymidy_synth_bact; 1. DR InterPro; IPR045097; Thymidate_synth/dCMP_Mease. DR InterPro; IPR023451; Thymidate_synth/dCMP_Mease_dom. DR InterPro; IPR036926; Thymidate_synth/dCMP_Mease_sf. DR InterPro; IPR000398; Thymidylate_synthase. DR InterPro; IPR020940; Thymidylate_synthase_AS. DR NCBIfam; TIGR03284; thym_sym; 1. DR PANTHER; PTHR11548:SF2; THYMIDYLATE SYNTHASE; 1. DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1. DR Pfam; PF00303; Thymidylat_synt; 1. DR PRINTS; PR00108; THYMDSNTHASE. DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1. DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Methyltransferase; Nucleotide biosynthesis; Transferase. FT CHAIN 1..297 FT /note="Thymidylate synthase" FT /id="PRO_0000140911" FT ACT_SITE 173 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 26 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 153..154 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 199..202 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 202 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 210 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 240..242 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT HELIX 4..19 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 21..24 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 28..36 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 40..43 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 45..47 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 53..55 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 59..70 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 76..80 FT /evidence="ECO:0007829|PDB:1F28" FT TURN 81..83 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 88..91 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 93..98 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 113..119 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 138..148 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 156..158 FT /evidence="ECO:0007829|PDB:1F28" FT TURN 162..164 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 173..181 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 191..202 FT /evidence="ECO:0007829|PDB:1F28" FT TURN 203..205 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 206..224 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 228..242 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 243..250 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 252..254 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 262..265 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 272..274 FT /evidence="ECO:0007829|PDB:1F28" FT HELIX 277..279 FT /evidence="ECO:0007829|PDB:1F28" FT STRAND 280..284 FT /evidence="ECO:0007829|PDB:1F28" SQ SEQUENCE 297 AA; 34362 MW; 985F6F870EF2A7B2 CRC64; MVNAEEQQYL NLVQYIINHG EDRPDRTGTG TLSVFAPSPL KFSLRNKTFP LLTTKRVFIR GVIEELLWFI RGETDSLKLR EKNIHIWDAN GSREYLDSIG LTKRQEGDLG PIYGFQWRHF GAEYIDCKTN YIGQGVDQLA NIIQKIRTSP YDRRLILSAW NPADLEKMAL PPCHMFCQFY VHIPSNNHRP ELSCQLYQRS CDMGLGVPFN IASYALLTCM IAHVCDLDPG DFIHVMGDCH IYKDHIEALQ QQLTRSPRPF PTLSLNRSIT DIEDFTLDDF NIQNYHPYET IKMKMSI //